Huntington’s Disease Successfully Treated in a World First

Hereditary disorder, Huntinton’s disease, destroys brain cells and worsens over time, leading to severe physical and mental decline. It slows down thought and movement and exhibits features of dementia, and Parkinson’s and motor neurone disease.

This disease impacts 30,000 people in the USA, and many more globally. It stems from a mutation in a gene called HTT, which turns a normal protein needed in the brain, the huntingtin protein, into a killer of neurons.

The DNA glitch doesn’t disable the protein, as most disease-causing mutations do, but creates a toxic version of it which hits people in their prime, beginning in a person’s 30s or 40s. The first symptoms are jerky movements and balance issues, but these progress over two decades to cognitive decline and difficulty in speaking and swallowing as the disease progresses until it is ultimately fatal.

Significantly, because the gene that causes Huntington’s runs in families, people affected by the disease have often watched loved ones struggle and die from it, too.

As CBS News Boston shares, the research team treated over two dozen patients with Huntington’s disease with a single treatment of gene therapy during a 12- to 20-hour surgical procedure on the brain, conducted slowly to avoid adverse reactions. The goal of this cutting edge treatment is to reduce levels of the toxic protein permanently, in a single dose. Encouraging results revealed that disease progression slowed in 75 percent of patients who received high doses.

Science emphasizes that this significantly slowed progress of the disease happened in a small clinical trial involving 12 people over three years who had received the treatment.

As with many other gene therapies, uniQure’s therapy relies on a harmless virus, the adeno-associated virus, to ferry a snippet of DNA into cells using real-time MRI scanning. But instead of encoding a gene, the DNA encodes a “microRNA” designed to stick onto the messenger RNA made by the mutant HTT gene so cells can‘t use this template to make the harmful huntingtin protein.

In other words, the shot sends a harmless virus encoded with instructions to turn off the production of the mutated protein, as the Smithsonian Magazine details.

BBC News highlights that the data shows scientists the treatment is saving brain cells. Levels of neurofilaments in spinal fluid – a clear sign of brain cells dying – should have increased by a third if the disease continued to progress, but was actually lower than at the start of the trial.

While none of the treated patients are being identified, one was medically retired and has returned to work, while others in the trial are still walking despite being expected to require a wheelchair to get around.

Professor Tabrizi is already working with a group of young people known to have the gene, but who don’t yet have symptoms. Her goal is to conduct the first prevention trial to see if the disease can be significantly delayed or even stopped completely.

Some scientists caution that this small study has yet to appear in a peer-reviewed journal, with the results so far only released in a statement by the company uniQure. They also point out that the treatment is likely to be costly, and must be infused directly into the brain so limiting who can receive it, but others are warmly welcoming this breakthrough.

“This is an immensely exciting development for the Huntington’s field,” the trial’s academic leader, neurologist Professor Sarah Tabrizi of University College London, said in a webcast for uniQure investors. Tabrizi suggests to Science that this treatment could be given to people with the HTT mutation before they develop symptoms and lose neurons, raising hopes that earlier treatment could prevent symptoms from ever emerging.

Moreover, she explains to BBC News that this treatment means that the decline typically expected in a year, would take four years after treatment, giving patients decades of “good quality life.” A positive Tabrizi also explains why the team is so enthusiastic about the results of the trial: “We never in our wildest dreams would have expected a 75% slowing of clinical progression.”

Welcoming the outcome as the result the team had been waiting for, Professor Ed Wild, consultant neurologist at the National Hospital for Neurology and Neurosurgery at University College London, said “There was every chance that we would never see a result like this, so to be living in a world where we know this is not only possible, but the actual magnitude of the effect is breathtaking, it’s very difficult to fully encapsulate the emotion.” He admitted to feeling “a bit teary” thinking about the impact it could have on families.

Scientific American enthuses that while the therapy, still in clinical trials and as yet unapproved, won’t be available for wider use anytime soon, this early success has given the Huntinton’s disease community measured hope after years of disappointments with unsuccessful new treatments, and therapies that can only treat symptoms, but do nothing to slow or halt the development of the disease.